This project was designed to study molecular events which may regulate gene expression during development. The work to date has focused primarily on expression of the murine alphafetoprotein (AFP) and metallothionein (MT) genes with particular emphasis on studying effects of glucocorticoids on mRNA levels in developing mice. Both AFP and MT genes are actively expressed in visceral yolk sac endoderm as well as in fetal and neonatal liver. We have found that in neonatal liver, glucocorticoids can induce a 3-5-fold decrease in AFP mRNA with a concomitant 5-10-fold increase in MT mRNA. However, during fetal development, glucocorticoids, even at teratogenic levels, did not result in alterations in AFP or MT mRNA levels in visceral yolk sac. Furthermore, hepatic AFP mRNA levels were unaffected by glucocorticoid and only after day 16 of gestation was there a small glucocorticoid-induced increase in hepatic MT mRNA. Since the actions of steroid hormones are thought to be mediated by specific receptor molecules in the target tissue, we analyzed developing visceral yolk sac and liver for glucocorticoid receptors. There was an 8-fold increase in receptor levels in visceral yolk sac (i.e. to 10,000 sites/cell) between days 9 and 14 of gestation. Receptor levels in fetal liver were constant (2-4 x 103 sites/cell) until day 16 and increased slightly to parturition. Hepatic receptor levels increased rapidly after birth reaching adult levels (i.e. 30,000 sites/cell) by days 10-14 post-partum. These results indicate that receptor levels may be limiting the glucocorticoid responses in early stages of fetal liver development, whereas, in visceral yolk sac, presence of receptor alone is not sufficient for response, at least as measured by changes in AFP and MT mRNA levels. Heavy metals (i.e. Cd+2, Zn+2, Cu+2) were found to induce an increase in MT mRNA in neonatal liver without affecting AFP gene expression.